Table 2.

Selected Isolated PIK3CA-Related Overgrowth Phenotypes by Affected Organ or Tissue

Organ or TissuePhenotypeComment
Brain/Head HMEG: brain overgrowth affecting 1 hemisphere w/or w/o cortical dysplasia
  • Cognitive & developmental disabilities
  • Seizures are common.
  • Focal neurologic deficits may be present.
  • May result in facial asymmetry
Focal cortical dysplasia 1
  • Types I, II, III 2
  • Overgrowth not as exaggerated as in HMEG
  • May → epilepsy, which may be refractory to medications if childhood onset
  • Cognitive impairment
DMEG: focal brain overgrowth w/cortical dysplasia; cortical dysplasia may be bilateral.
  • Developmental delay
  • Frequently severe epilepsy 3 w/in 1st few mos of life
  • Focal neurologic deficits may be present.
Facial infiltrating lipomatosis
  • Unilateral hypertrophy of soft tissues of the face (most commonly cheek) w/underlying fat infiltration 4, 5
  • May incl bony hypertrophy
Limb Hemihyperplasia
  • May incl whole limb, part of limb, or only hand or foot (acral overgrowth)
  • May involve soft tissue, muscle, &/or bone
Macrodactyly
  • May affect ≥1 digits on hand or foot
  • May involve soft tissue, muscle &/or bone
Fibroadipose vascular anomaly
  • Fibrofatty tissue w/dilated veins (phlebectasia) replaces muscle fibers.
  • Low-flow venous or lymphatic malformation 6
  • May present as painful lump, typically of the gastrocnemius
  • May be assoc w/ankle dorsiflexion & calf contracture
Macrodactyly or macrodystrophia lipomatoma
  • Fibroadipose tissue enlargement & bony overgrowth w/in a nerve territory (e.g., upper or lower limbs, hands & feet) w/↑ length & circumference of peripheral nerve
  • Growth can be static (proportionate) or progressive (disproportionate).
Lymphatics 7 Isolated lymphatic malformations: dilated vascular channels lined by lymphatic endothelial cellsFluid-filled cysts usually grow proportionally w/growth of affected person; may → pain &/or morbidity if they are infiltrative.
Vascular 7 Vascular malformationsIncl capillary, venous, or mixed malformations
Skin
  • Benign lichenoid keratosis
  • Epidermal nevi
  • Seborrheic keratosis
Skin lesions are typically benign.

Overgrowth can affect any part of the body depending on the distribution of the PIK3CA pathogenic variant in various tissues and organs.

DMEG = dysplastic megalencephaly; HMEG = hemimegalencephaly

1.

Often characterized histologically as having dysplastic neurons, balloon cells, and lamination disorganization

2.

Type I: isolated focal lesions with architectural abnormalities
Type II: isolated focal lesions with architectural and dysmorphic abnormalities
Type III: cortical disorganization associated with or adjacent to other principal lesions

3.

Seizures are typically partial and may include infantile spasms, tonic seizures, or electroclinical features of Ohtahara syndrome.

4.

May be associated with precocious dental development, macrodontia, hemimacroglossia, protuberances on the tongue and buccal mucosa, and mucosal neuromas

5.
6.

Rare high-flow variants due to excessively muscularized venous channels. Organizing thrombi may be present.

7.

Overgrowth of capillary, lymphatic, and venous channels is sometimes referred to as CLVM (capillary lymphatic venous malformations), in which dilated lymphatic channels are combined with venous and capillary components.

From: PIK3CA-Related Overgrowth Spectrum

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